Acute thrombotic obstruction of the blood flow in a coronary artery precipitates myocardial infarction. The loss of heart muscle in the necrotic zone and the compromised function of the remaining viable cardiomyocytes of the peri-necrotic region initiate a series of events that, if unopposed, frequently lead to adverse remodeling of the heart chamber, precipitating heart failure. The mainstay of treatment of acute myocardial infarction (MI) associates rapid restoration of a patent coronary artery either mechanically or through thrombolytic and anti-platelet therapies, and administration of agents that reduce oxygen consumption and unload the heart muscle. The wide use of this therapeutic strategy has led to significant reductions in both morbidity and mortality after acute MI [White, H. D et al., 2008]. Still, the clinical and social burden of ischemic heart disease is unacceptably high and the efficacy of additional anti-thrombotic therapies is often mitigated by the increased risk of hemorrhagic events. Thus, efforts are being directed towards targeting other pathophysiological pathways, particularly those involved in post-ischemic cardiac remodelling [Shah, A. M et al., 2011].
The immune system becomes activated in response to myocardial damage. Shortly after ischemia, the damaged tissue exposes ligands that are recognized by components of the innate immune system, which leads to its activation. For example, non-myosin heavy chain type II A and C are exposed following ischemia/reperfusion injury and recognized by natural IgM antibodies, leading to activation of mannan binding lectin and serum complement, which aggravates tissue injury. C-reactive protein (CRP), a short pentraxin acute-phase protein, also binds to damaged tissue and activates the complement, leading to aggravation of tissue injury in the setting of acute MI 13. In contrast, long pentraxin 3, a molecule that limits complement activation plays a cardioprotective role in this setting. The acute inflammatory response also leads to the mobilization and recruitment of innate immune cells. Few hours after the ischemic insult, neutrophils are actively recruited into the ischemic tissue and contribute to tissue inflammation and cardiovascular injury through the production of inflammatory mediators, reactive oxygen species and various proteases [Granger, D. N. et al, 1995 and Vinten-Johansen, J 2004]. The wave of neutrophil infiltration is followed by the mobilization and recruitment of monocytes. Recent studies have shed new light on the mechanisms of monocytes recruitment and life cycle in the setting of acute MI, and suggested differential pathogenic or protective roles for Ly6Chi and Ly6Clo monocytes, respectively, in cardiac remodeling and preservation of heart function [Nahrendorf, M., et al, 2007 and Leuschner, F., et al, 2012]. Despite this increasing knowledge, the utility of targeting the immune response in this setting is still uncertain as revealed by the lack of efficacy of complement inhibition in patients with acute MI [Mahaffey, K. W., et al, 2003; Granger, C. B., et al, 2003; Armstrong, P. W., et al, 2007 and Eikelboom, J. W et al, 2007]. Thus, a better characterization of the determinants of the immune response following ischemic injury and the mechanisms by which they contribute to tissue damage is required in order to fill the existing gap of knowledge that limits clinical translation, and design efficient therapeutic strategies for future use in humans.